Multi-Dimensional Chromatography Modulator with Variable Modulation Period

ABSTRACT

A multi-dimensional gas chromatograph for analyzing compounds in a sample during a single run is disclosed. The multi-dimensional gas chromatograph includes a first column, a second column, and a modulator disposed between the first column and the second column. The modulator modulates at (i) a first modulation period over a first time period during the run and (ii) a second modulation period over a second time period during the run later than the first time, the second modulation period being different than the first modulation period.

CROSS REFERENCE TO RELATED APPLICATIONS

This PCT application claims priority to U.S. Provisional Application No.62/793,509, filed on Jan. 17, 2019, the disclosure of which isconsidered part of the disclosure of this application and is herebyincorporated by reference in its entirety.

TECHNICAL FIELD

This disclosure relates to the field of gas chromatography, includingComprehensive Multi-Dimensional Gas Chromatography (GC×GC),Comprehensive Multi-Dimensional Gas Chromatography-High Resolution MassSpectrometry (GC×GC-HRMS), Comprehensive Multi-Dimensional GasChromatography-Time-of-Flight Mass Spectrometry (GC×GC-ToF-MS), and thelike.

BACKGROUND

Gas chromatography is conventionally used to separate and analyzecompounds in a variety of applications and across a number ofdisciplines. Traditional gas chromatography may involve the combinationof a sample, or mixture of analytes, to be tested with a carrier gas(e.g., helium or hydrogen) within a column to form an effluent. As theeffluent moves through the column, various analytes may be separatedfrom one another due to a variety of factors, such as, for example, flowcharacteristics, mass of the analyte, etc. Upon exiting the column, theseparated analytes may be detected and analyzed.

When two or more analytes of a sample have similar characteristics, itmay be difficult to separate such analytes because they may tend to moveat similar velocities through the column such that a sufficient amountof separation does not occur. To address the foregoing and improve theresolution of the analysis, rather than using a single column, atechnique has been implemented whereby at least portions of the effluentare periodically injected into a second column, whereby the secondcolumn may possess one or more different characteristics than the firstcolumn, and the effluent is detected by a detector at the end of thesecond column. This is generally known as comprehensive two-dimensional(or multi-dimensional) gas chromatography (GC×GC).

In a comprehensive two-dimensional gas chromatography system, the firstcolumn and the second column may be coupled to one another by amodulator. The modulator may be capable of modulating the effluent manytimes for the duration of an analysis. The modulation period may bedefined as the time it takes for the modulator to sample and inject theeffluent from the first column into the second column. The modulator mayrepeat the modulation period during the entirety of a run or analysis ofthe GC×GC system, hundreds or even thousands of time.

The modulation rate of a GC×GC system, for example, a low duty cycleGC×GC system, may influence the collection and analysis of qualitativeand quantitative information about the analyte. For example, amodulation period that is too long may result in analytes beinginsufficiently sampled from the first column and peaks or analytes maybe lost or undetected by the modulator. Conversely, a modulation periodthat is too short may result in an issue referred to as “wrap-around.”Wrap-around may occur when peaks from a modulation period are retainedfor so long in the second column that they elute in a subsequentmodulation period where they may coelute with peaks from the subsequentmodulation, resulting in degradation of the quality of thechromatographic separation and ability to identify analytes.Accordingly, there may be an optimal modulation period based on thewidth of the peak eluting from the first column. The optimal modulationperiod may provide a sufficient number of modulations across the widthof the peak eluting from the first column to provide quantitativeresults for low duty cycle modulators and little reduction in firstdimension chromatographic resolution for all modulators, but not anexcessive number of short duration modulations which may result inwrap-around.

Additionally, the optimal modulation period may change over the courseof a GC×GC run as early-eluting peaks may have narrower peaks thanlater-eluting peaks. This may be particularly evident toward the end ofa GC×GC run if an isothermal hold is used at the end of the run due totemperature limitations of the columns. Accordingly, it may be desirablefor GC×GC systems to account for changing optimal modulation periodsover the course of a GC×GC run.

SUMMARY

One aspect of the disclosure provides a two-dimensional gaschromatograph for analyzing compounds in a sample during a single run.The two-dimensional gas chromatograph includes a first column, a secondcolumn, and a modulator disposed between the first column and the secondcolumn. The modulator modulates at (i) a first modulation period over afirst time period during the run and (ii) a second modulation periodover a second time period during the run later than the first timeperiod, the second modulation period being different than the firstmodulation period.

Implementations of the disclosure may include one or more of thefollowing features. In some implementations, the second modulationperiod may be longer than the first modulation period. The modulator maybe operating at a low duty cycle.

At least one of the first modulation period or the second modulationperiod may be configured to provide a sufficient number of modulationsacross a width of a peak eluting from the first column to providequantitative results and little reduction in first dimensionchromatographic resolution for the modulator. The sufficient number ofmodulations may be configured to avoid wrap-around on a chromatogram.

The two-dimensional gas chromatograph may include an injector configuredto inject a sample into the first column. The modulator may beconfigured to sample the sample and inject the sample into the secondcolumn. The two-dimensional gas chromatograph may include a detectorconfigured to receive and detect the sample.

Another aspect of the disclosure provides a method for detectingcompounds in a sample during a single run using a two-dimensional gaschromatograph having an injector, a first column, a second column and amodulator disposed between the first column and the second column. Themethod includes injecting a sample into the first column, passing afirst portion of the sample into the modulator, and modulating, by themodulator, the first portion of the sample at a first modulation periodover a first period of time. Modulating at the first modulation periodover the first period of time includes sampling the first portion of thesample and injecting the first portion of the sample into the secondcolumn. The method includes detecting the first portion of the sample ata detector. The method includes passing a second portion of the sampleinto the modulator, and modulating, by the modulator, the second portionof the sample at a second modulation period different than the firstmodulation period over a second period of time. Modulating at the secondmodulation period over the second period of time includes sampling thesecond portion of the sample and injecting the second portion of thesample into the second column. The method includes detecting the secondportion of the sample at the detector.

Implementations of the disclosure may include one or more of thefollowing features. In some implementations, the second modulationperiod may be longer than the first modulation period. The modulator maybe operating at a low duty cycle.

At least one of the first modulation period or the second modulationperiod may be configured to provide a sufficient number of modulationsacross a width of a peak eluting from the first column to providequantitative results and little reduction in first dimensionchromatographic resolution for the modulator. The sufficient number ofmodulations may be configured to avoid wrap-around on a chromatogram.

Sampling the first portion of the sample and injecting the first portionof the sample into the second column may occur multiple times over thefirst period of time. Sampling the second portion of the sample andinjecting the second portion of the sample into the second column mayoccur multiple times over the second period of time.

Another aspect of the disclosure provides a modulator for atwo-dimensional gas chromatograph for analyzing compounds in a sampleduring a single run. The modulator is configured to perform a methodcomprising modulating a first portion of a sample from a first column ata first modulation period over a first period of time. Modulating at thefirst modulation period over the first period of time includes samplingthe first portion of the sample and injecting the first portion of thesample into a second column. The modulator is configured to modulate asecond portion of the sample from the first column at a secondmodulation period over a second period of time. Modulating at the secondmodulation period over the second period of time includes sampling thesecond portion of the sample and injecting the second portion of thesample into the second column.

Implementations of the disclosure may include one or more of thefollowing features. In some implementations, the modulator may bedisposed between the first column and the second column of thetwo-dimensional gas chromatograph.

The second modulation period may be longer than the first modulationperiod.

The modulator may be operating at a low duty cycle.

At least one of the first modulation period or the second modulationperiod may be configured to provide a sufficient number of modulationsacross a width of a peak eluting from the first column to providequantitative results and little reduction in first dimensionchromatographic resolution for the modulator, and the sufficient numberof modulations may be configured to avoid wrap-around on a chromatogram.

The details of one or more implementations of the disclosure are setforth in the accompanying drawings and the description below. Otheraspects, features, and advantages will be apparent from the descriptionand drawings, and from the claims.

DESCRIPTION OF DRAWINGS

FIG. 1 is a schematic view of an exemplary comprehensive two-dimensionalgas chromatography (GC×GC) system; and

FIG. 2 is a flowchart of an exemplary method for detecting compounds ina sample during a single analysis using the GC×GC system of FIG. 1.

Like reference symbols in the various drawings indicate like elements.

DETAILED DESCRIPTION

The following description of the various embodiments is merely exemplaryin nature and is in no way intended to limit the invention, itsapplication or uses. For brevity, the disclosure hereof will illustrateand describe a two-dimensional gas chromatography system in variousexemplary embodiments. Based on the foregoing, it is to be generallyunderstood that the nomenclature used herein is simply for convenienceand the terms used to describe the invention should be given thebroadest meaning by one of ordinary skill in the art.

With reference to the figures, where like reference symbols indicatelike elements, a comprehensive two-dimensional gas chromatography(GC×GC) system 10 is generally shown schematically at FIG. 1. The GC×GCsystem 10 includes an injector 12, a first column (or capillary) 14, asecond column (or capillary) 16, a modulator 18, and a detector 20. TheGC×GC system 10 includes a main oven 22, and the main oven 22 may houseat least the injector 12, the first column 14, the second column 16, themodulator 18, and the detector 20.

The injector 12 may be configured to receive a sample 24 and a carriergas 26. The sample 24 may be injected into the injector 12 via aninjection device 28, such as, for example, a syringe, an automatedinjection device, or any other suitable means. The carrier gas 26 may becontained in a container 30, such as a tank. The sample 24 may be anysuitable analyte, such as, for example, petroleum, fragrances,drug-related liquids, etc. The carrier gas 26 may be any suitable gas,such as, for example, an inert gas such as helium, an unreactive gassuch as nitrogen, etc. The injector 12 may mix the sample 24 and thecarrier gas 26 to form an effluent 34, and the injector 12 may injectthe effluent 34 into the first column 14.

The first column 14 and the second column 16 may be wound in a generallycircular configuration. The first column 14 may extend from the injector12 to the modulator 18, and the second column 16 may extend from themodulator 18 to the detector 20. In some implementations, the firstcolumn 14 and the second column 16 may have different characteristicsfrom each other. In one example, the first column 14 may be longer, havea greater diameter, and/or contain a different stationary phase than thesecond column 16. In another example, the first column 14 may be shorterand/or have a smaller diameter than the second column 16.

The modulator 18 may be configured to receive the sample 24 from thefirst column 14 and perform modulation on the sample 24 over a period oftime referred to as a modulation period. The modulation process mayinclude at least the steps of sampling the sample 24 and injecting thesample 24 into the second column 16. In some implementations, themodulation process includes an additional step of focusing the sample 24prior to injecting the sample 24 into the second column 16. Themodulation period is the time it takes for the modulator 18 to completethe modulation process, including the aforementioned steps.

The modulator 18 may be configured to, e.g., programmed to, have aplurality of modulation periods during a single run or analysisperformed by the GC×GC system 10. For example, a single analysisperformed by the GC×GC system 10 may be the time it takes for the GC×GCsystem 10 to analyze the entirety of the sample 24. As another example,a single analysis performed by the GC×GC system 10 may be any suitabletime duration as defined by an operator of the GC×GC system 10. In someimplementations, the modulator 18 modulates with a first modulationperiod over a first time period during the analysis, and the modulator18 modulates with a second modulation period over a second time periodduring the analysis later than the first time. The second modulationperiod may be different than the first modulation period. For example,the second modulation period may be longer than the first modulationperiod. The duration of the modulation period may rely on a variety offactors, including, for example, a sufficiency of sampling the sample24, a desire to eliminate wrap-around of signal peaks in a chromatogram,etc. In some implementations, the modulator 18 has a plurality ofmodulation periods during a single analysis performed by the GC×GCsystem 10, and the modulator 18 continuously or semi-continuouslychanges from one of the plurality of modulation periods to another ofthe plurality of modulation periods throughout the analysis, asdetermined by a variety of factors including, for example, sample type,temperature, duration of the analysis, etc.

The modulator 18 may be any suitable type of modulator, such as, forexample, a thermal modulator, a valve-based modulator, etc. While asingle modulator 18 is depicted in FIG. 1, it should be understood thatany suitable number of modulators 18 may be used. The modulator 18 maybe operated at any suitable duty cycle, such as, for example, a low dutycycle, a mid-range duty cycle, a high duty cycle, etc.

The detector 20 may be configured to receive the sample 24 from thesecond column 16. The detector 20 may detect a plurality of data aboutthe sample 24, including, for example, retention time, signal (orintensity), etc. The detector 20 may be any suitable type of detector,such as, for example, a flame ionization detector (FID), an electroncapture detector (ECD), an atomic emission detector (AED), a sulfurchemiluminescence detector (SCD), a nitrogen chemiluminescence detector(NCD), a nitrogen phosphorous detector (NPD), etc. Additionally oralternatively, a mass spectrometry system may be hyphenated to the GC×GCsystem 10 and used as the detector 20.

A computing device 32 may be in communication with the detector 20 andmay receive data about the sample 24 from the detector 20. The computingdevice 32 may be any suitable device, such as, for example, a computer,a laptop, a tablet, a smartphone, etc. The computing device 32 mayprocess the data about the sample 24 and output a chromatogram. Thechromatogram may be a three-dimensional plot displaying three variables:retention time from the first column 14 (e.g., in a first dimension)along the X-axis, signal (or intensity) along the Y-axis, and retentiontime from the second column 16 (e.g., in a second dimension) along theZ-axis. Additionally or alternatively, the chromatogram may be a contourplot displaying retention time from the first column 14 (e.g., in thefirst dimension) along the X-axis, retention time from the second column16 (e.g., in the second dimension) along the Y-axis, and contours and/orcolor scaling indicating signal peaks. The computing device 32 may alsoprogram the modulator 18, specifically, by instructing the modulator 18when to switch from a first modulation period to a second modulationperiod.

In view of the foregoing, a method 100 for detecting compounds in asample during a single analysis using the exemplary GC×GC system 10, asillustrated in FIG. 2, will now be described.

First, the sample 24 is prepared and placed into a suitable form, e.g.,a liquid form, a gas form, etc. Next, the sample is injected into theinjector 12 where it mixes with the carrier gas 26 to form the effluent34. As will be appreciated, the injector 12 may be a hot piece of quartz(silica) that vaporizes the sample 24, allowing it to mix with thecarrier gas 26. Thereafter, the sample 24 is injected into the firstcolumn 14 at step 102, where it is then separated based on at leastselectivity of the stationary phase in the first column 14. It will beappreciated that, as previously described, the effluent 34 may be amixture including the sample 24 and the carrier gas 26. Accordinglyreferences to the sample 24 at step 102, and hereinafter, may includethe sample 24 as part of the effluent 34.

At step 104, the sample 24, i.e., a first portion of the sample 24,exits the first column 14 and passes into the modulator 18. Themodulator 18 may be set at step 106 to either a first modulation periodor a second modulation period. For example, if it is early in theanalysis, the modulator 18 may be set to the first modulation period andif it is later in the analysis, the modulator 18 may be set to thesecond modulation period. While two modulation periods are described, itis to be understood that any suitable number of modulation periods maybe used. For illustrative purposes, the method 100 will be describedwith the modulator 18 set to the first modulation period first, and thenswitched to the second modulation period after.

Next, the modulator 18 modulates the first portion of the sample 24 withthe first modulation period at step 108. During a first time period ofthe analysis with the modulator 18 being set to the first modulationperiod, the modulator 18 samples the first portion of the sample 24 andinjects the first portion of the sample 24 into the second column 16 atstep 112, where it is then separated at step 114 based on at leastselectivity of the stationary phase in the second column 16. Thereafter,the first portion of the sample 24 exits the second column 16 and isdetected at step 116 by the detector 20. The detector 20 then sends dataat step 118 about the first portion of the sample 24 to the computingdevice 32. This process may occur multiple times (e.g., tens, hundreds,or thousands of times) over the course of the first time period.

As soon as the modulator 18 injects the first portion of the sample 24into the second column 16, the modulator 18 is ready to receive anotherportion of the sample 24. After modulating with the first modulationperiod at step 108 over the first time period of the analysis, themodulator 18 may be switched to the second modulation period, forexample, at a later time in the analysis. The modulator 18 may receive asecond portion of the sample 24 at step 104. At this point, themodulator 18 may be set at step 106 to the second modulation period, andthe modulator 18 may modulate over a second time period of the analysis.During the second time period where the modulator 18 is set to thesecond modulation period, the modulator 18, at step 110, samples thesecond portion of the sample 24 and injects the second portion of thesample 24 into the second column 16 at step 112, where it is thenseparated at step 114 based on at least selectivity of the stationaryphase in the second column 16. Thereafter, the second portion of thesample 24 exits the second column 16 and is detected at step 116 by thedetector 20. The detector 20 then sends data at step 118 about thesecond portion of the sample 24 to the computing device 32, where achromatogram, e.g., a three-dimensional chromatogram, is created. Thisprocess may occur multiple times (e.g., tens, hundreds, or thousands oftimes) over the course of the second time period.

After the sample 24 is injected into the first column 14 at step 102,steps 104-118 of the method 100 may be repeated throughout an entireanalysis of the GC×GC system 10. That is, the modulator 18 may continueto modulate portions of the sample 24 received from the first column 14and send them through the second column 16 to the detector 20 until theentirety of the sample 24 has been eluted.

A number of implementations have been described. Nevertheless, it willbe understood that various modifications may be made without departingfrom the spirit and scope of the disclosure. Accordingly, otherimplementations are within the scope of the following claims.

What is claimed is:
 1. A multi-dimensional gas chromatograph foranalyzing compounds in a sample during a single run, the chromatographcomprising: a first column; a second column; and a modulator disposedbetween the first column and the second column, the modulator modulatingat (i) a first modulation period over a first time period during the runand (ii) a second modulation period over a second time period during therun later than the first time period, the second modulation period beingdifferent than the first modulation period.
 2. The multi-dimensional gaschromatograph of claim 1, wherein the second modulation period is longerthan the first modulation period.
 3. The multi-dimensional gaschromatograph of claim 1, wherein the modulator is operating at a lowduty cycle.
 4. The multi-dimensional gas chromatograph of claim 1,wherein at least one of the first modulation period or the secondmodulation period are configured to provide a sufficient number ofmodulations across a width of a peak eluting from the first column toprovide quantitative results and little reduction in first dimensionchromatographic resolution for the modulator.
 5. The multi-dimensionalgas chromatograph of claim 4, wherein the sufficient number ofmodulations are configured to avoid wrap-around on a chromatogram. 6.The multi-dimensional gas chromatograph of claim 1, further comprisingan injector configured to inject a sample into the first column.
 7. Themulti-dimensional gas chromatograph of claim 6, wherein the modulator isconfigured to sample the sample and inject the sample into the secondcolumn.
 8. The multi-dimensional gas chromatograph of claim 7, furthercomprising a detector configured to receive and detect the sample.
 9. Amethod for detecting and quantifying compounds in a sample during asingle run using a multi-dimensional gas chromatograph having aninjector, a first column, a second column and a modulator disposedbetween the first column and the second column, the method comprising:injecting a sample into the first column; passing at least a firstportion of the sample into the modulator; modulating, by the modulator,the first portion of the sample at a first modulation period over afirst period of time, modulating at the first modulation period over thefirst period of time including: sampling the first portion of thesample; and injecting the first portion of the sample into the secondcolumn; detecting the first portion of the sample at a detector; passinga second portion of the sample into the modulator; modulating, by themodulator, the second portion of the sample at a second modulationperiod different than the first modulation period over a second periodof time, modulating at the second modulation period over the secondperiod of time including: sampling the second portion of the sample; andinjecting the second portion of the sample into the second column; anddetecting the second portion of the sample at the detector.
 10. Themethod of claim 9, wherein the second modulation period is longer thanthe first modulation period.
 11. The method of claim 9, wherein themodulator is operating at a low duty cycle.
 12. The method of claim 9,wherein at least one of the first modulation period or the secondmodulation period are configured to provide a sufficient number ofmodulations across a width of a peak eluting from the first column toprovide quantitative results and little reduction in first dimensionchromatographic resolution for the modulator.
 13. The method of claim12, wherein the sufficient number of modulations are configured to avoidwrap-around on a chromatogram.
 14. The method of claim 12, whereinsampling the first portion of the sample and injecting the first portionof the sample into the second column occur multiple times over the firstperiod of time.
 15. The method of claim 12, wherein sampling the secondportion of the sample and injecting the second portion of the sampleinto the second column occur multiple times over the second period oftime.
 16. A modulator for a multi-dimensional gas chromatograph foranalyzing compounds in a sample during a single run, the modulatorconfigured to perform a method comprising: modulating a first portion ofa sample from a first column at a first modulation period over a firstperiod of time, including: sampling the first portion of the sample; andinjecting the first portion of the sample into a second column; andmodulating a second portion of the sample from the first column at asecond modulation period different than the first modulation period overa second period of time, including: sampling the second portion of thesample; and injecting the second portion of the sample into the secondcolumn.
 17. The modulator of claim 16, wherein the modulator is disposedbetween the first column and the second column of the multi-dimensionalgas chromatograph.
 18. The modulator of claim 16, wherein the secondmodulation period is longer than the first modulation period.
 19. Themodulator of claim 16, wherein the modulator is operating at a low dutycycle.
 20. The modulator of claim 16, wherein at least one of the firstmodulation period or the second modulation period are configured toprovide a sufficient number of modulations across a width of a peakeluting from the first column to provide quantitative results and littlereduction in first dimension chromatographic resolution for themodulator, and the sufficient number of modulations are configured toavoid wrap-around on a chromatogram.